The role of the polyamines in cell growth and replication will be investigated by following changes in intracellular levels of the polyamines and in the activities of their biosynthetic enzymes, over the course of the cell cycle. Regulation of polyamine biosynthesis will be studied using inhibitors of nucleic acid and protein synthesis. The effect of polyamine antimetabolites on cell cycle traverse will be studied also. To provide a basis for the rational design of improved polyamine antimetabolites the structural requirements for binding to the active site of ornithine decarboxylase will be investigated. These quantitative structure-activity correlations will examine inhibition of ornithine decarboxylase by a series of structural analogs of ornithine. Finally, the potential applicability of polyamine antimetabolites to the chemotherapy of intracranial tumors will be explored using in vitro and in vivo colony forming efficiency assays and increased life span studies.